PROJECT SUMMARY Candidate: My career goal is to improve the wellbeing of older adults with multiple chronic conditions and polypharmacy by developing and rigorously testing rational strategies to improve medication prescribing practices; and to become an independent clinician investigator and national leader in Geriatric Cardiology. This area is particularly relevant for me as a heart failure cardiologist, as I care for older adults who almost universally have multiple chronic conditions and polypharmacy. My track record as an emerging leader in this area is evidenced by multiple lead- and senior-author manuscripts, 4 grants as the Principal Investigator including a GEMSSTAR, my position as the Founding Director of the Weill Cornell Heart Failure with Preserved Ejection (HFpEF) Program for the Aging, and my role as the Chair of the American College of Cardiology Geriatric Cardiology Section Early Career Professionals Working Group. Mentors and Environment: This project will be conducted under the mentorship of 4 well-funded investigators who will contribute their complementary expertise in Geriatrics (Mark Lachs), Geriatric Cardiology (Mathew Maurer), Implementation Science (Monika Safford), and N-of-1 trials (Ian Kronish). Advisors in deprescribing, shared decision making, and biostatistics will provide additional content expertise to ensure the success of the proposed project and catalyze my career development. This project will take place within the supportive environment of Weill Cornell Medicine, which has demonstrated a deep commitment to my development as a clinician-investigator for the past several years. Mentored Research Project: Despite its role as an integral part of patient-centric and goal-concordant prescribing practice, deprescribing is seldom incorporated into clinical practice due to several barriers. To improve patient-centered medication management, there is a need to develop processes that can overcome these barriers. The objective of this proposal is to determine whether N- of-1 trials?as a pragmatic patient-centered approach to medication optimization that can overcome key barriers of deprescribing? can lead to increased patient confidence regarding the decision to continue or discontinue a medication. To achieve this, I will: 1) determine key features of a feasible and pragmatic protocol for deprescribing N-of-1 trials using a stakeholder-engaged iterative design approach; and 2) determine the preliminary effectiveness of an adapted N-of-1 protocol on patient decision confidence and deprescribing, and 3) determine the facilitators and barriers of implementing an adapted N-of-1 protocol into real-world clinical practice by conducting a type-1 hybrid effectiveness-implementation trial. I will achieve these aims by using - blocker in heart failure with preserved ejection fraction (HFpEF) as a prototype for older adults with multimorbidity and polypharmacy. This proposal will inform a future multicenter randomized controlled trial focused on improving patient-reported outcomes, and provide a formative opportunity for me to obtain the knowledge and skills necessary to become a leading researcher on patient-centered medication management.